Noradrenergic (NE) and serotonergic (5-HT) neurons of the brainstem have widespread and dense axonal projections to all areas of the cerebral cortex. This project will attempt to characterize and relate several morphologic and biochemical features of these divergent systems. Initial immunohistochemical studies have show that the NE axons pass tangentially through the cortical grey matter and, in the rat, are readily interrupted by a small frontal lesion. To further characterize and quantify this phenomenon, levels of the transmitters and their metabolites will be determined following several different cortical lesions and survival times. By conducting a similar analysis in the pig, we shall test whether this type of cortical pathway is found in the gyrencephalic brain. To clarify the mechanism by which NE and 5-HT axons influence cortical neurons (synaptic vs. diffusion), the ultrastructural features of these axons will be studied by EM immunocytochemistry and will be related to biochemical parameters of transmitter release. Processes of NE neurons that extend into the ventricles will be characterized by transmission and scanning E.M. The time course of biochemical parameters of NE axon degeneration after axotomy will be analyzed to clarify the conditions under which the monoamine innervation of adult cortex will regenerate.